Lian Mao

Real-World Outcomes of Paliperidone Palmitate Compared to Daily Oral Antipsychotic Therapy in Schizophrenia: A Randomized, Open-Label, Review Board–Blinded 15-Month Study

OBJECTIVE The Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study compared the effects of once-monthly paliperidone palmitate with daily oral antipsychotics on treatment failure in adults with schizophrenia. METHOD The PRIDE study is a 15-month, randomized, multicenter study (May 5, 2010, to December 9, 2013) of adult subjects with a DSM-IV diagnosis of schizophrenia and a history of incarceration. Subjects were randomly assigned to once-monthly paliperidone palmitate injections or daily oral antipsychotics (randomly assigned from 7 acceptable, prespecified oral antipsychotics) for 15 months. The primary end point was time to first treatment failure, defined as arrest/incarceration; psychiatric hospitalization; suicide; treatment discontinuation or supplementation due to inadequate efficacy, safety, or tolerability; or increased psychiatric services to prevent hospitalization. Time to first treatment failure was determined by a blinded event-monitoring board and analyzed with the Kaplan-Meier method. RESULTS In this study, 450 patients were randomly assigned, and 444 were included in the intent-to-treat population. Paliperidone palmitate was associated with significant delay in time to first treatment failure versus oral antipsychotics (hazard ratio, 1.43; 95% CI, 1.09-1.88; log rank P = .011). Observed treatment failure rates over 15 months were 39.8% and 53.7%, respectively. Arrest/incarceration and psychiatric hospitalization were the most common reasons for treatment failure in the paliperidone palmitate and oral antipsychotic groups (21.2% vs 29.4% and 8.0% vs 11.9%, respectively). The 5 most common treatment-emergent adverse events for the paliperidone palmitate treatment group were injection site pain (18.6% of subjects), insomnia (16.8%), weight increased (11.9%), akathisia (11.1%), and anxiety (10.6%). CONCLUSIONS In a trial designed to reflect real-world management of schizophrenia, once-monthly paliperidone palmitate demonstrated superiority compared to oral antipsychotics in delaying time to treatment failure. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT01157351.

An assessment of emergent tardive dyskinesia and existing dyskinesia in patients receiving long-acting, injectable risperidone: Results from a long-term study

INTRODUCTION Treatment-emergent tardive dyskinesia (TD) can be a serious side effect of antipsychotic treatment. Atypical antipsychotics are associated with a lower risk for TD than are conventional agents. A long-acting atypical antipsychotic, with more stable blood levels and lower peak blood levels than an oral formulation, may provide differential benefit regarding side effects, including movement disorders. This analysis assessed TD by defined research criteria in patients receiving long-acting, injectable risperidone. METHODS Clinically stable subjects with schizophrenia or schizoaffective disorder participated in a 50-week, open-label trial of long-acting, injectable risperidone. TD was studied by defined research criteria (Schooler, N.R., Kane, J.M., 1982. Research diagnosis for tardive dyskinesia. Arch. Gen. Psychiatry. 39, 486-487; Americal Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders, fourth ed. American Psychiatric Association, Washington, DC). The severity of dyskinesia and other movement disorders were rated by the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS ESRS dyskinesia data were available for 662 patients. Five of 530 subjects without dyskinesia at baseline (0.94%) met the predefined criteria for emergent persistent TD during therapy. Based on either exposure to study medication or Kaplan-Meier analysis, the 1-year rate was 1.19%. Among the 132 subjects with dyskinesia at baseline, the mean score on the ESRS physicians exam for dyskinesia improved significantly at endpoint (-2.77; P<0.0001), regardless of anticholinergic drug use. (P=0.243 for patients with versus without anticholinergic drug use.) CONCLUSIONS In this open-label study, treatment with long-acting risperidone was associated with a low rate of emergent persistent TD. Significant improvement in existing dyskinesias was noted. The TD rate reported here is consistent with other reports of atypical antipsychotics and substantially lower than with conventional antipsychotics.

Treatment effect with paliperidone palmitate compared with oral antipsychotics in patients with recent-onset versus more chronic schizophrenia and a history of criminal justice system involvement.

Long‐acting injectable antipsychotics (APs) are not well studied in recent‐onset schizophrenia. This exploratory analysis of a study designed to reflect real‐world schizophrenia, as defined by patients, interventions and outcomes, compared relative treatment effect between once‐monthly paliperidone palmitate (PP) and daily oral APs in patients with recent‐onset or chronic illness

A pragmatic analysis comparing once-monthly paliperidone palmitate versus daily oral antipsychotic treatment in patients with schizophrenia.

BACKGROUND Persons with schizophrenia often come in contact with the criminal justice system (CJS). This analysis of subjects with schizophrenia and a history of contact with the CJS estimated and compared mean cumulative function (MCF) of treatment failure events when treated with paliperidone palmitate (PP) or oral antipsychotics (OAs). All events identified during the full study period of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) trial were evaluated. METHODS Subjects were randomly assigned to flexibly dosed, monthly, injectable PP (78-234 mg) or daily OA in a 15-month prospective, open-label, multicenter US study (May 5, 2010-December 9, 2013). Subjects could continue participation after a treatment failure event. Multiple treatment failures in individual subjects were analyzed as recurrent events. Analyses estimated MCF of treatment failure events and MCF of institutionalizations (arrests, incarcerations, or psychiatric hospitalizations) during the 15-month study period. RESULTS The ITT population included 226 (PP) and 218 (OA) subjects, of whom 41.2% and 40.4%, respectively, completed 15 months of follow-up. The MCF of treatment failures and institutionalizations differed significantly in favor of PP compared with OA (P=0.007 and P=0.005, respectively). Overall, TEAEs were reported by 86.3% of subjects in the PP group and 81.7% in the OA group. CONCLUSIONS This pragmatic analysis suggests that, compared with OA, PP is not only more effective in delaying median time to treatment failure, but it also reduces the number of treatment failures and institutionalizations per person-year follow-up. CLINICAL TRIALS REGISTRATION Clinicaltrials.gov identifier: NCT01157351.

Comparison of long-acting and oral antipsychotic treatment effects in patients with schizophrenia, comorbid substance abuse, and a history of recent incarceration: An exploratory analysis of the PRIDE study.

INTRODUCTION Comorbid substance abuse is known to blunt response to treatment for underlying psychiatric disorders, but it has not been investigated in schizophrenia when comparing the effects of long-acting injectable antipsychotics with those of oral antipsychotics. METHODS This exploratory analysis compared once-monthly paliperidone palmitate (PP1M) with daily oral antipsychotics on time to treatment failure in patients with schizophrenia and a history of incarceration. Subjects were stratified into substance abuse (reported substance or alcohol misuse in the past 30days on the baseline Addiction Severity Index-Lite Version and/or met criteria for a current MINI diagnosis of a substance abuse disorder) and nonabuse cohorts. RESULTS In the substance abuse cohort, treatment failure was observed in 56.2% (73/130) and 64.2% (86/134) of subjects in the PP1M and oral antipsychotic groups, respectively. For the nonabuse cohort, treatment failure was observed in 36.5% (35/96) and 53.6% (45/84) of subjects in the PP1M and oral antipsychotic groups, respectively. Median (95% confidence interval [CI]) time to first treatment failure was 291 (179-428) days and 186 (94-296) days in the PP1M and oral antipsychotic groups, respectively. Median (95% CI) time to first treatment failure was >450 and 284 (147 to >450) days in the respective treatment groups. CONCLUSION Greater treatment effects were evident with PP1M compared with oral antipsychotics in both cohorts. The observed beneficial effect of PP1M was attenuated in the substance-abuse cohort, further reinforcing both the need for and value of continued research to optimize patient care in these complex patient populations.